Joanna Melia, MD, on S1P Receptor Modulators in Treating IBD

Sphingosine 1-phosphate (S1P) receptor modulators could be the next big thing in the treatment and management of moderate to severe ulcerative colitis (UC), Joanna Melia, MD, said during her presentation at the Advances in Inflammatory Bowel Disease Regionals virtual regional meeting on September 30.

Dr Melia is a gastroenterologist specializing in UC, Crohn disease (CD), microscopic colitis, collagenous colitis, and Celiac disease, at the John Hopkins Bayview Medical Center in Baltimore, Maryland.

While highlighting the benefits of S1P modulators in general, Dr Melia’s primary focus was on ozanimod, the first S1P receptor modulator approved by the US Food and Drug Administration (FDA) in May 2021.

She shed light on the placebo-controlled, phase 3 clinical trial, TRUE NORTH, that evaluated the efficacy of ozanimod as induction and maintenance therapy in adult patients with active UC. The primary outcome was clinical remission. At week 10, significantly more patients achieved clinical remission with ozanimod compared with placebo (18.4% vs 6.0%). On the secondary key points, as well, patients in the ozanimod group fared better than those in the placebo group on clinical response (47.8% vs 25.9%), endoscopic improvement (27.3% vs 11.6%), and mucosal healing (12.6% vs 3.7%)

At week 52, 37% of patients in the ozanimod treatment group compared with 18.5% in the placebo group reached the primary endpoint of clinical remission and on the secondary endpoints of clinical response (60.0% vs 41.0%), endoscopic improvement (45.7% vs 26.4%), clinical remission (31.7% vs 16.7%), and mucosal healing (29.6% vs 14.1%).

Adverse events observed were anemia, nasopharyngitis, headaches, arthralgia, and elevated gamma-glutamyltransferase. “Cardiovascular events were rare,” Dr Melia stated.

In the double-blind, placebo-controlled phase 2 trial called TOUCHSTONE, 16.0% of patients treated with ozanimod achieved clinical remission at 8 weeks vs 6.0% of patients on placebo. The results for secondary endpoints were also better for ozanimod group vs placebo group – clinical response (57.0% vs 37.0%), mucosal healing (34.0% vs 12.0%), and histologic remission (22.0% vs 11.0%).

In this trial, researchers found no significant differences in adverse events between the 2 treatment groups. “Minor side effects include asymptomatic bradycardia and major side effects may be hepatotoxicity and macular edema,” Dr Melia noted.

She believes that “S1P receptor modulators really do represent a novel therapeutic target.” However, she cautioned against prescribing ozanimod among patients with cardiovascular arrythmias and those who have a history of macular edema. Also, she noted, “It would be safe to expect liver enzyme elevation and lymphopenia post-medication.”

Upon considering important pretreatment screening and multiple safety factors, the overall safety profile of S1P receptor modulators remains favorable. “Symptom relief is possible as soon as 2 weeks into medication,” Dr Melia said. “The results are solid.”

—Priyam Vora

Reference:

Melia J, S1P receptor modulators: How they work and how to use them. Presented at: Advances in Inflammatory Bowel Disease regional meeting; September 30, 2022. Virtual.